Osteoarthritis (OA) is a whole-joint disorder characterized by progressive cartilage degradation and chronic synovial inflammation, in which macrophages play a central role. Using single-cell RNA sequencing of human and mouse synovial tissues, we identified a pronounced expansion of macrophages during OA progression, with nearly ubiquitous expression of the chemokine CXCL16. These CXCL16+ macrophages exhibited a pro-inflammatory phenotype and were strongly associated with synovitis. To exploit t...